This PA11-112 application is proposed for the National Institute on Aging. The objective of the research project is to understand better the extent to which ovarian removal affects long-term cognitive functioning in older women. The findings may be useful to the over 300,000 US women who undergo prophylactic ovarian removal annually as existing research has not been conclusive. Reasons for inconsistent findings have been the lack of considerations for use and timing of hormone therapy, diagnoses of cardiovascular diseases and cancer, depressive symptoms as a mediator, and well-matched comparison groups. The project is comprised of two studies. The Study I sample is an all-female older-adult twin cohort and the Study II sample is healthy women free of signs or symptoms of cardiovascular disease who enrolled in longitudinal clinical trials. Study I specific aims include examining the extent oophorectomy is associated with cognitive impairment, the extent this relation is influenced by genetic or early environmental factors, the extent timing of oophorectomy and hormone therapy predicts cognitive impairment, and the extent that depression mediates these relations. Study II specific aims include examining the extent that ovarian removal, time since surgery, and hormone use and its timing is associated with cognitive domain performance over time and the extent that depression mediates the association especially for learning and memory. These aims are studied using unmatched case-control design, co-twin control design, regression that adjusts for relatedness of twins, linear regression, and models that use difference scores for repeated measures. Cardiovascular diseases and cancer history are controlled for in both studies. The training outlined in the proposal is well-suited for the fellowship applicant, who is an advanced- year dual degree candidate for a doctorate in clinical psychology (clinical aging track) and a master in public health (biostatistics/epidemiology track). Supporters for this project, who are well-respected experts in cognitive functioning and diseases, sex hormones, gynecology, and biostatistics, will guide this interdisciplinary project and the applicant's scholarly development. The project duration is 13 months, which is the balance of the applicant's predoctoral training. The applicant serves as the PD/PI and will be the only trainee closely associated with the project. Aside from the proposed project, the research training program includes relevant statistical and clinical training to provide psychotherapy to clients of different ages, culture, and presenting problems (e.g., depressive symptoms, chronic illnesses, etc.). PUBLIC HEALTH RELEVANCE: The findings from this research training program will provide health care professionals and women and their families with empirical information about the potential risks of oophorectomy and surgical menopause on long-term cognitive functioning. This is a public health concern as older adults are already vulnerable to cognitive performance declines and clinically significant impairment. Better research can inform interventions, improve patient expectations of outcomes, and ultimately control economic impact of the cognitive dysfunction among the elderly.